Oligonucleotides can modulate a vast variety of cellular functions and therefore represent a promising alternative to conventional therapies. Among the different oligonucleotides with therapeutic potential are aptamers, transcription factor-binding decoy oligonucleotides, ribozymes, triplex-forming oligonucleotides, immunostimulatory CpG motifs, antisense oligonucleotides, small interfering RNAs (siRNAs), long non coding RNAs (lncRNAs), mRNAs, microRNAs, and antimiRs. Their two main advantages over protein- or peptide-based strategies are the high specificity for their target and being non-immunogenic. However, despite these advances, a major bottleneck to the development of nucleic acid-based strategies for treatment and prevention of human diseases is the inefficient means to effectively deliver these oligonucleotides into the desired target cells. Although viral vectors have been widely used to transfer nucleic acids into cells, they bear an inherent risk for the patient to encounter severe immunological responses or even develop cancer. As a result of these problems there has been an urgent need in recent years to the development of non-viral delivery systems. Currently, liposomes and cationic polymers are used as a standard tool to transfect cells in vitro. However, these procedures lack significant efficiency in primary cells and are highly toxic rendering them mostly unfeasible for in vivo applications.